Radicals, from carboxylates

The generation of radicals from carboxylate ions at the anode (Section 2.17.6, p. 115), and their coupling to form new carbon-carbon bonds is illustrated by the synthesis of hexacosane (Expt 5.11). The method has been usefully applied to the preparation of esters of long-chain carboxylic acids, from which of course the free acids may be prepared by hydrolysis. 

Another way that has potential for the generation of perfluoroalkyl radicals from carboxylic acids is the use of Barton esters. However, unlike the situation for their hydrocarbon analogs, fluorinated thiohydroxamate esters have thus far only been able to be prepared in situ [65]. 

The generation of oxygen-centered radicals from carboxylic acids and alcohols with the tandem reagent, PhI(OAc)2-l2, is an established practice... 

Barton, D. H. R., Crich, D., Motherwell, W. B. The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters a new method for the generation of carbon radicals from carboxylic acids. Tetrahedron 1985, 41,3901-3924. 

Radicals from Carboxylic Acids. Carboxy radicals appear to be involved in three venerable reactions in preparative carbohydrate chemistry, the Ruff degradation, the Hunsdiecker reaction and the Kolbe electrolysis. 

Although the vast majority of publications involving Barton esters have involved the generation of carbon-centered radicals from carboxylic acids, the 0-acylthiohy-droxamate decarboxylative protocol has also been extended to other substrates. 

Several useful synthetic methodologies are based on the generation of the oxygen-centered radicals from carboxylic acids and the (diacetoxyiodo)benzene-iodine system [613-617]. In particular, a direct conversion of 2-substituted benzoic acids 566 into lactones 567 via oxidative cyclization induced by [bis(acyloxy)iodo]arene/iodine has been reported (Scheme 3.224) [613,614]. 

Startg. selenoimidate, tri-n-butyltin hydride, and AIBN in toluene heated at 110° for 3-6 h - product. Y 84% (after oxidation with DDQ). F.e. and 4-chromanones, also generation of imidoyl radicals from carboxylic acid thioamides via S-stannyl thio-imidates, s. M.D. Bachi, D. Denenmark, J. Am. Chem. Soc. Ill, 1886-8 (1989). 

A hydroxymethyl group can be introduced (ArH —> ArCH20H) by several variations of this method. Alkylation of these substrates can also be accomplished by generating the alkyl radicals in other ways from hydroperoxides and FeS04, from alkyl iodides and H2O2—Fe V from carboxylic acids and lead tetraacetate, or from the photochemically induced decarboxylation of carboxylic acids by iodoso-benzene diacetate. 

This group has examples of many types of acids derived from aliphatic, aromatic and heterocyclic radicals, with carboxylic, phenolic or sulfonic or related functional substituents. Individually indexed acids are ... 

A radical tandem cyclization, consisting of two radical carbocyclizations and a heterocoupling reaction, has been achieved by electrolysis of unsaturated carboxylic acids with different coacids. This provides a short synthetic sequence to tricyclic products, for example, triquinanes, starting from carboxylic acids which are accessible in few steps (Scheme 6) [123]. The selectivity for the formation of the tricyclic, bi-cyclic, and monocyclic product depending on the current density could be predicted by applying a mathematical simulation based on the proposed mechanism. 

This reaction resembles decarboxylation of carboxylates during electrode one-electron oxidation (Kolbe reaction). Kolbe reaction also consists of one-electron oxidation, decarboxylation, and culminates in dimerization of alkyl radicals just after their formation at the electrode surface. When the sulfate radical acts as a one-electron oxidant, the caboradical dimerization is hampered. The radicals can be used in preparative procedures. One typical example is alkylation of heterocyclic nitrogen bases (Minisci et al. 1983). This difference between Kolbe reaction and the reaction with the help of a dissolved electrode (the sulfate radical) deserves some explanation. The concentration of the one-electron oxidation products in the electrode vicinity is significantly higher than that in the bulk of the solution. Therefore, in the case of anode-impelled reactions, the dimerization of radicals produced from carboxylates proceeds easily. Noticeably, 864 secures the single electron nature of oxidation more strictly than an anode. In electrode reactions, radical intermediates can... 

A further general route to the 1,2-dicarbonyl system involves the oxidation of a-ketols (acyloins) (cf. the preparation of benzil from benzoin, Expt 6.143). The acyloins may be prepared from carboxylate esters by a radical coupling reaction involving the use of finely divided sodium metal in anhydrous ether, benzene, or toluene.144... 

The first step in the formation of the dihydrofullerenes is electron transfer and proton loss. The C02 loss from carboxyl radicals is well known [233], The so-formed aminomethyl radical then adds to C6o- The final step is the abstraction of hydrogen from the environment (Scheme 23). 

From the practical point of view, alkylation of heteroaromatics with Barton decarboxylation of A-acyloxy-2-thiopyridones (17), prepared from carboxylic acids and Af-hydroxy-2-thiopyridone, is very useful, since it can be used for various kinds of carboxylic acids such as sugars and nucleosides [23-26]. This reaction comprises of the initial homolytic cleavage of the N-0 bond in A-acyloxy-2-thiopyridone to form an acyloxyl radical and PyS , (3-cleavage of the acyloxyl radical to generate an alkyl radical and C02, addition to the electron-deficient position of heteroaromatics by the alkyl radical to form the adduct, and finally, abstraction of a hydrogen atom from the adduct by PyS , as shown in eq. 5.10. 

Treatment of O-acyl esters (2) with l,l-dichloro-2,2-difluoroethylene provides a,a-difluorocarboxylic acids (37) through photolysis, followed by the hydrolysis of the adducts (36) with AgN03 (eq. 8.17) [53]. Eq. 8.18 shows the preparation of a-keto carboxylic acids (40) from carboxylic acids, by means of the radical addition to ethyl acrylate, oxidation to the sulfoxides by mCPBA, the Pummerer reaction with... 

Finally, radicals can fragment to a smaller radical and a normal molecule in a process that is the reverse of addition. As an example, radicals derived from carboxylic acids eliminate carbon dioxide very rapidly. 

C. Loss of a carboxyl radical from metastable ions ... 

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